Chemotherapy constitutes one of the major therapeutic approaches for the treatment of cancer, along with surgery and radiotherapy. However, the usefulness of commonly used anti-cancer drugs is severely limited by their toxicity towards normal tissues, particularly the rapidly proliferating cells of the gastrointestinal tract and bone marrow. In addition, these drugs are affected by the mechanisms of multi-drug resistance.
Nucleoside analogs have been studied for their antitumor effects. For example, the cytosine nucleoside analogs 5-azacytidine (azacitidine), 5-aza-2′-deoxycytidine (decitabine), 1-β-D-arabinofuranosyl-5-azacytosine (fazarabine), 1-β-D-arabinofuranosylcytosine (cytosine arabinoside, cytarabine, Ara-C) and dihydro-5-azacytidine (DHAC) have been used clinically in cancer treatment.
There is evidence, however, that such agents may be harmful and/or ineffective in some settings. Moreover, both azacytidine and decitabine have the common side effect of inducing nausea, vomiting, diarrhea and myelosuppression that limit doses and duration of treatment (Christman J K, (2002). Oncogene 21(35): 5483-5495).
As such, there is a continued need to develop new treatments for cancer.
The present description refers to a number of documents, the content of which is herein incorporated by reference in their entirety.